INCREASED PRODUCTION OF ROS BY PLATELETS IN EXPERIMENTAL CIRRHOSIS
(Abstract release date: 05/21/15)
EHA Library. Romecin Duran P. 06/12/15; 102936; PB1961
Disclosure(s): Hospital Universitario Virgen de la Arrixaca-EspañaHematology
Dr. Paola Alejandra Romecin Duran
Contributions
Contributions
Abstract
Abstract: PB1961
Type: Publication Only
Background
Despite the endogenous coagulopathy of cirrhosis, some patients experience venous thromboembolism. Previous studies in experimental cirrhosis by bile duct ligation (BDL) have shown a platelet hyperactivity, similar to humans with biliary cirrhosis disease (Clin.Sci., 2007,112(3):167-74). In these experiments we have found abnormal intracellular Ca2+ homeostasis and alterations in the metabolism of homocysteine (Hcy) that may contribute to those platelet alterations (J. Hepatology 2009, S280). The role of ROS in this platelet hyperactivity is not known.
Aims
Investigate agonist-induced production of ROS in platelets of bile duct ligated rats and the effects of chronic folic acid treatment (an essential cofactor in the metabolism of homocysteine (Hcy)).
Methods
Cirrhosis was induced in rats by bile duct ligation (BDL) and sham-operated rats were used as control. The experiments were performed after 21 days (without ascites) and 28 days (BDL group with ascites) after surgery. Platelet rich plasma aggregation in response to ADP (5µM) was analyzed using a lumiaggregometer. To analyze ROS, by fluorescence spectroscopy, platelet suspensions were washed and incubated with CM-H2DCFDA acetyl ester and stimulated with thrombin (0.3U/mL), ADP (5µM) and homocysteine (Hcy, 50-200µM). In some experiments, sham and BDL rats were treated with folic acid (8 mg/Kg/day in drinking water).
Results
Platelet stimulation with thrombin and Hcy induced an increase in ROS production that was of greater magnitude in platelet from BDL rats than in control. Ascites reduced aggregation response and increased ROS production. Chronic treatment with folic acid decreased more platelet aggregation and ROS production in BDL than in control group.
Summary
Folic acid show antiaggregant actions in cirrhotic rats due in part to attenuation of a high ROS production and might be used for prevention of venous thromboembolism in liver cirrhosis. But, with proper control, due to the folic acid reduces platelet aggregation excessively in cirrhosis with ascites and can produce increased maintenance of gastrointestinal bleeding due to portal hypertension characteristic of this disease.
Keyword(s): Cirrhosis, Homocysteine, Platelet, Reactive oxygen species
Session topic: Publication Only
Type: Publication Only
Background
Despite the endogenous coagulopathy of cirrhosis, some patients experience venous thromboembolism. Previous studies in experimental cirrhosis by bile duct ligation (BDL) have shown a platelet hyperactivity, similar to humans with biliary cirrhosis disease (Clin.Sci., 2007,112(3):167-74). In these experiments we have found abnormal intracellular Ca2+ homeostasis and alterations in the metabolism of homocysteine (Hcy) that may contribute to those platelet alterations (J. Hepatology 2009, S280). The role of ROS in this platelet hyperactivity is not known.
Aims
Investigate agonist-induced production of ROS in platelets of bile duct ligated rats and the effects of chronic folic acid treatment (an essential cofactor in the metabolism of homocysteine (Hcy)).
Methods
Cirrhosis was induced in rats by bile duct ligation (BDL) and sham-operated rats were used as control. The experiments were performed after 21 days (without ascites) and 28 days (BDL group with ascites) after surgery. Platelet rich plasma aggregation in response to ADP (5µM) was analyzed using a lumiaggregometer. To analyze ROS, by fluorescence spectroscopy, platelet suspensions were washed and incubated with CM-H2DCFDA acetyl ester and stimulated with thrombin (0.3U/mL), ADP (5µM) and homocysteine (Hcy, 50-200µM). In some experiments, sham and BDL rats were treated with folic acid (8 mg/Kg/day in drinking water).
Results
Platelet stimulation with thrombin and Hcy induced an increase in ROS production that was of greater magnitude in platelet from BDL rats than in control. Ascites reduced aggregation response and increased ROS production. Chronic treatment with folic acid decreased more platelet aggregation and ROS production in BDL than in control group.
Summary
Folic acid show antiaggregant actions in cirrhotic rats due in part to attenuation of a high ROS production and might be used for prevention of venous thromboembolism in liver cirrhosis. But, with proper control, due to the folic acid reduces platelet aggregation excessively in cirrhosis with ascites and can produce increased maintenance of gastrointestinal bleeding due to portal hypertension characteristic of this disease.
Keyword(s): Cirrhosis, Homocysteine, Platelet, Reactive oxygen species
Session topic: Publication Only
Abstract: PB1961
Type: Publication Only
Background
Despite the endogenous coagulopathy of cirrhosis, some patients experience venous thromboembolism. Previous studies in experimental cirrhosis by bile duct ligation (BDL) have shown a platelet hyperactivity, similar to humans with biliary cirrhosis disease (Clin.Sci., 2007,112(3):167-74). In these experiments we have found abnormal intracellular Ca2+ homeostasis and alterations in the metabolism of homocysteine (Hcy) that may contribute to those platelet alterations (J. Hepatology 2009, S280). The role of ROS in this platelet hyperactivity is not known.
Aims
Investigate agonist-induced production of ROS in platelets of bile duct ligated rats and the effects of chronic folic acid treatment (an essential cofactor in the metabolism of homocysteine (Hcy)).
Methods
Cirrhosis was induced in rats by bile duct ligation (BDL) and sham-operated rats were used as control. The experiments were performed after 21 days (without ascites) and 28 days (BDL group with ascites) after surgery. Platelet rich plasma aggregation in response to ADP (5µM) was analyzed using a lumiaggregometer. To analyze ROS, by fluorescence spectroscopy, platelet suspensions were washed and incubated with CM-H2DCFDA acetyl ester and stimulated with thrombin (0.3U/mL), ADP (5µM) and homocysteine (Hcy, 50-200µM). In some experiments, sham and BDL rats were treated with folic acid (8 mg/Kg/day in drinking water).
Results
Platelet stimulation with thrombin and Hcy induced an increase in ROS production that was of greater magnitude in platelet from BDL rats than in control. Ascites reduced aggregation response and increased ROS production. Chronic treatment with folic acid decreased more platelet aggregation and ROS production in BDL than in control group.
Summary
Folic acid show antiaggregant actions in cirrhotic rats due in part to attenuation of a high ROS production and might be used for prevention of venous thromboembolism in liver cirrhosis. But, with proper control, due to the folic acid reduces platelet aggregation excessively in cirrhosis with ascites and can produce increased maintenance of gastrointestinal bleeding due to portal hypertension characteristic of this disease.
Keyword(s): Cirrhosis, Homocysteine, Platelet, Reactive oxygen species
Session topic: Publication Only
Type: Publication Only
Background
Despite the endogenous coagulopathy of cirrhosis, some patients experience venous thromboembolism. Previous studies in experimental cirrhosis by bile duct ligation (BDL) have shown a platelet hyperactivity, similar to humans with biliary cirrhosis disease (Clin.Sci., 2007,112(3):167-74). In these experiments we have found abnormal intracellular Ca2+ homeostasis and alterations in the metabolism of homocysteine (Hcy) that may contribute to those platelet alterations (J. Hepatology 2009, S280). The role of ROS in this platelet hyperactivity is not known.
Aims
Investigate agonist-induced production of ROS in platelets of bile duct ligated rats and the effects of chronic folic acid treatment (an essential cofactor in the metabolism of homocysteine (Hcy)).
Methods
Cirrhosis was induced in rats by bile duct ligation (BDL) and sham-operated rats were used as control. The experiments were performed after 21 days (without ascites) and 28 days (BDL group with ascites) after surgery. Platelet rich plasma aggregation in response to ADP (5µM) was analyzed using a lumiaggregometer. To analyze ROS, by fluorescence spectroscopy, platelet suspensions were washed and incubated with CM-H2DCFDA acetyl ester and stimulated with thrombin (0.3U/mL), ADP (5µM) and homocysteine (Hcy, 50-200µM). In some experiments, sham and BDL rats were treated with folic acid (8 mg/Kg/day in drinking water).
Results
Platelet stimulation with thrombin and Hcy induced an increase in ROS production that was of greater magnitude in platelet from BDL rats than in control. Ascites reduced aggregation response and increased ROS production. Chronic treatment with folic acid decreased more platelet aggregation and ROS production in BDL than in control group.
Summary
Folic acid show antiaggregant actions in cirrhotic rats due in part to attenuation of a high ROS production and might be used for prevention of venous thromboembolism in liver cirrhosis. But, with proper control, due to the folic acid reduces platelet aggregation excessively in cirrhosis with ascites and can produce increased maintenance of gastrointestinal bleeding due to portal hypertension characteristic of this disease.
Keyword(s): Cirrhosis, Homocysteine, Platelet, Reactive oxygen species
Session topic: Publication Only
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